The pathogenicity of group A streptococci is being studied to gain further insight into the mechanisms of infections and poststreptococcal sequelae. Proposed and continuing projects include the following: 1. The structure of M proteins, the protective antigens of group A streptococci, is being studied. New techniques such as detergent extraction are being investigated for obtaining M proteins for further purification. Structural analyses are being carried on to determine the composition and amino acid sequence of M proteins from "rheumatogenic" and "nephritogenic" streptococci. 2. An in vitro model for the mechanism of rheumatic heart disease was developed with cultured cardiac myofibers as target cells for lymphocytes "sensitized" to various streptococcal antigens in order to determine the role of cell-mediated immunity in rheumatic heart disease. In order to relate the cytotoxic lymphocyte phenomenon to autoimmunity, it is necessary to use inbred animals. Therefore, an inbred mouse model is proposed here. The in vitro chromium-51 release assay system will be re-examined and defined. The streptococcal protoplast membrane protein which has been shown to cross react with heart-reactive autoantibody in rheumatic patients' sera will be tested for its capacity to generate the heart destructive T-lymphocyte. The T-lymphocytes will be passively transferred to syngeneic, irradiated mice to see if the initial inflammatory signs marked by the infiltration of lymphocytes in the target tissue can be observed. The passive transfer will be also examined by "homing" of the cytotoxic T-lymphocytes, radiolabeled prior to the transfer, specifically to the target organ. BIBLIOGRAPHIC REFERENCES: Wittner, M.K. and Fox, E.N. 1977. Homologous and heterologous protection of mice with group A streptoccal M protein vaccines. Infect. Immun. 15, 104-108. Sabet, T.Y., Kelly, P.L. and Fox, E.N. 1977. Infant rats inoculated intranasally with group B streptococci; induction of bacteremia and meningitis. Abs. Ann. Meeting Am. Soc. Microbiol., in press.